Table 4.
ORACLE-MS efficacy: key MRI endpoints [94]
| Placebo [n = 206] | Cladribine tablets 3.5 mg/kg [n = 206] | Cladribine tablets 5.25 kg/mg [n = 204] | |
|---|---|---|---|
| Time to conversion to clinically definite MS (Poser criteria) | |||
| Risk reduction, % | 67 | 62 | |
| HR (95% CI) | 0.33 (0.21–0.51) | 0.38 (0.25–0.58) | |
| p value vs. placebo | < 0.0001 | < 0.0001 | |
| Cumulative percentage probability of clinically definite MS conversion, % | 38.0 | 14.0 | 15.9 |
| New or persisting T1 Gd+ lesions | |||
| Median cumulative number of lesions (IQR) | 2.0 (0.0–5.0) | 0.0 (0.0–1.0) | |
| Treatment group comparison: cladribine/placebo, ratio (95% CI)a | 0.108 (0.55–0.210)b | ||
| Risk reduction vs. placebo, % | 89.3 | ||
| New or enlarging T2 lesions | |||
| Median cumulative number of lesions (IQR) | 2.0 (0.0–8.0) | 0.0 (0.0–2.0) | |
| Treatment group comparison: cladribine/placebo, ratio (95% CI)a | 0.212 (0.152–0.295) | ||
| Risk reduction vs. placebo, % | 78.8 | ||
| Combined unique active lesions | |||
| Median cumulative number of lesions (IQR) | 4.0 (1.0–13.5) | 1.0 (0.0–3.0) | |
| Treatment group comparison: cladribine/placebo, ratio (95% CI)a | 0.157 (0.098–0.251) | ||
| Risk reduction vs. placebo, % | 84.3 |
Data are for the double-blind treatment period (i.e. from randomization to the end of the double-blind period, which was at 96 weeks, or earlier if a diagnosis of MS was made)
CI confidence interval, Gd + gadolinium-enhancing, HR hazard ratio, IQR interquartile range, MRI magnetic resonance imaging, MS multiple sclerosis
aFrom the analysis of the cumulative number of lesions, using a negative binomial model with treatment, region, treatment × region, and baseline lesion count as covariates, and the log number of scans as an offset variable
bp < 0.0001 versus placebo from the Wald Chi-square test